biostudies-literatureUnknown25(1)Riess AUniversitätsklinikum TübingenDeutsche ForschungsgemeinschaftMulvihill-Smith Syndrome (MSS) is a clinically complex and genetically unsolved nano-rare disorder with only 12 patients reported in the literature. Most patients (91%) have immunological impairments, succumb to infection, and might develop cancer later in life. Its pathogenesis remains elusive and therapeutic options are limited. We used single-cell MULTI-omics (sc-MULTI-omics), combining transcriptomics (gene expression, TCR, and BCR repertoire) and proteogenomic (Cellular Indexing of Transcriptomes and Epitopes by Sequencing; CITE-seq), to decipher the pathophysiology of nano-rare disease patient. We report a new patient who is a 16-year-old girl. She had an increased leukocyte counts and typical manifestations of MSS such as short stature, older appearance, multiple pigmented nevi, micFunctional & integrative genomics101https://www.ebi.ac.uk/biostudies/studies/S-EPMC12064584biostudies-literaturesc-MULTI-omics approach in nano-rare diseases: understanding the pathophysiological mechanism of Mulvihill-Smith Syndrome.PMC12064584Selting ASSingh YCasadei NLysenkov VOssowski SRoggia CRiess ORiess Afalsesc-MULTI-omics approach in nano-rare diseases: understanding the pathophysiological mechanism of Mulvihill-Smith Syndrome.Mulvihill-Smith Syndrome (MSS) is a clinically complex and genetically unsolved nano-rare disorder with only 12 patients reported in the literature. Most patients (91%) have immunological impairments, succumb to infection, and might develop cancer later in life. Its pathogenesis remains elusive and therapeutic options are limited. We used single-cell MULTI-omics (sc-MULTI-omics), combining transcriptomics (gene expression, TCR, and BCR repertoire) and proteogenomic (Cellular Indexing of Transcriptomes and Epitopes by Sequencing; CITE-seq), to decipher the pathophysiology of nano-rare disease patient. We report a new patient who is a 16-year-old girl. She had an increased leukocyte counts and typical manifestations of MSS such as short stature, older appearance, multiple pigmented nevi, mic2025-01-01T00:00:00Z2025 May2026-04-08T19:45:49.893Z2026-04-08T14:26:18.244ZS-EPMC120645844034359110.1007/s10142-025-01608-y